Heterotopic heart allografts and congeneric xenografts survive, i.e., continue to beat, for 6 months when implanted into the body cavity of the snail Biomphalaria glabrata, the main intermediate host of Schistosoma mansoni in the New World. However, xenografts from other genera, except those from Helisoma trivolvis, are rapidly destroyed, regardless of donor-recipient taxonomic (and presumably phylogenetic) distance. Although these results have enhanced our understanding of the fate of tissue transplants in molluscs, several questions remain with respect to the nature of the cellular response against grafts, the types of nonself determinants recognized by the recipient's hemocytes, and the relationship of donor-recipient phylogenetic distance and xenograft fate. Consequently, cellular responses against allografts will be compared to those against isografts. Next, an attempt will be made to alter the fate of allografts and xenografts by altering or masking cell surface molecules. To discern between physiological unsuitability and immunological rejection as the mechanism of xenograft death, agarose- encapsulated xenografts will be implanted. Finally, heart implants from two genera which are closely related to Helisoma will be carried out to further elucidate the phylogenetic relationship between H. trivolvis and B. glabrata. In addition to the histological techniques previously employed, an in vitro model of graft destruction will be developed, and an actin-specific staining method will be used to assess graft fate.